Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract disease, and the standard prevention strategy in Japan is limited to high-risk infants. Nirsevimab provides protection against medically attended (MA) RSV infection in healthy late-preterm and term infants and was approved in Japan in 2024. This study estimates the cost-effectiveness of universal immunization with nirsevimab in an all-infant population from the Japanese public healthcare payer perspective.A static decision analytic model, able to track costs and health outcomes in a cohort of infants, was adapted to the Japanese setting. The standard of care, palivizumab, administered to high-risk infants, was compared with nirsevimab administrated to all infants in the first year, and an additional increased dose of nirsevimab (200 mg) in the second season for high-risk infants. Differences in costs and quality-adjusted life years (QALYs) were captured considering RSV-related MA health events requiring inpatient hospitalizations, emergency room visits, and primary care visits, as well as RSV-related complications. Sensitivity and scenario analyses were conducted to explore the robustness and uncertainty of the study.Assuming a price of ¥45,000 for nirsevimab, universal immunization with nirsevimab was found to be cost-effective with an incremental cost-effectiveness ratio (ICER) of ¥4,537,256/QALY. At the Japanese willingness-to-pay threshold of ¥5,000,000, the economically justifiable price was ¥45,496. Using the societal perspective, the ICER decreased to ¥1,695,635/QALY. Nirsevimab has a substantial public health impact on RSV disease burden, reducing approximately 50% of RSV-associated health events in an all-infant population.The analysis demonstrated that universal prophylaxis strategy with nirsevimab would significantly reduce the health and economic burden associated with RSV among infants in Japan. At the assumed price, nirsevimab can provide a cost-effective prophylaxis option against RSV infection in an all-infant population not limited to infants born prematurely or with high risk.